Tuberculosis (TB) is one of the most widespread infectious diseases and a leading cause of death for adults worldwide. Although much attention has focused on treatment and prevention of human TB (presumably due to Mycobacterium tuberculosis), human TB from animal origin (zoonotic TB due to Mycobacterium bovis) is an important and re-emerging public health concern in developing countries. A large number of traditional livestock keepers (pastoralists) combined with poor public health infrastructure, limited TB control measures for cattle and animal products, and a large immunocompromised human population due to HIV/AIDS, make Africa particularly vulnerable to the health impacts of zoonotic TB. Zoonotic TB infection is significant, as M. bovis is naturally resistant to pyrazinamide, a first-line TB treatment drug. Both M. bovis and M. tuberculosis (M. tb) have demonstrated the ability to move between animal (including wildlife) and human populations. Recently M. bovis was also suspected in human-to-human spread. These new discoveries are challenging traditional assumptions about the transmission of TB. Human infections with M. bovis are believed to result from close contact with cattle (aerosol transmission), ingestion of contaminated milk or meat, or exposure during slaughter. Mycobacterium can survive for long periods (up to 400 days) in water, 6 and infective forms can be deposited into water sources by animals or people from fecal, urinary, oral, or respiratory routes. Nowhere is the potential for waterborne transmission more important than in Africa, where water scarcity is forcing people, domestic animals, and wildlife to share shrinking, poor quality water sources. RELEVANCE: The primary objective of this project is to describe the epidemiology, risk factors, and transmission dynamics of M. tuberculosis and M. bovis between humans and animals in a well-defined rural population in Tanzania (the Ruaha region). We will determine whether under-recognized animal and environmental transmission routes are contributing to transmission of M. tuberculosis and M. bovis and the impact on human health.